Combining a PARP inhibitor with targeted radiation therapy for neuroendocrine tumors
Phase 1 Trial of PARP Inhibitor Combined With 177Lu-DOTA-Octreotate Peptide Receptor Radionuclide Therapy (PRRT) in Patients With Metastatic NeuroEndocrine Tumor
This study is testing if combining a new cancer drug with targeted radiation therapy can safely help people with advanced pancreatic or midgut neuroendocrine tumors.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 24 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Peter MacCallum Cancer Centre, Australia Academic / other |
| Drugs / interventions | immunotherapy |
| Locations | 1 site (Melbourne, Victoria) |
| Trial ID | NCT05053854 on ClinicalTrials.gov |
What this trial studies
This phase 1 dose-escalation study evaluates the safety and tolerability of talazoparib in combination with 177Lu-DOTA-Octreotate peptide receptor radionuclide therapy (PRRT) in patients with metastatic pancreatic or midgut neuroendocrine tumors (NET). Participants will receive one cycle of 177Lu-DOTA-Octreotate alone, followed by three cycles of the combination therapy. The study aims to determine the optimal dosing and assess any potential side effects of this treatment approach.
Who should consider this trial
Good fit: Ideal candidates are adults over 18 with histologically confirmed Grade 2 NET from pancreatic or intestinal origin and suitable for PRRT.
Not a fit: Patients with significant uncorrected carcinoid heart disease or discordant FDG-avid disease may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced neuroendocrine tumors.
How similar studies have performed: While combining PARP inhibitors with radionuclide therapy is a novel approach, similar studies have shown promise in other cancer types.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria:
1. Patient must be \> or equal to18 years of age and must have provided written informed consent.
2. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
3. Histologically confirmed Grade 2 NET, Ki-67 of 3-20%, from pancreatic or intestinal origin.
4. Patient clinically suitable for PRRT
5. Tumor SSR uptake on GaTate PET/CT higher than liver activity, ≥ modified Krenning 3 score
6. No discordant FDG-avid disease on FDG PET/CT
7. No evidence of significant uncorrected carcinoid heart disease
8. Patients must be willing and able to comply with the protocol for the duration of the study including undergoing treatment, scheduled assessments
9. Patients must have adequate bone marrow, hepatic and renal function defined as:
* Haemoglobin ≥100 g/L
* Absolute neutrophil count ≥1.5x109/L
* Platelets ≥150 x109/L
* Total bilirubin ≤1.5 x upper limit of normal (ULN)
* Aspartate transaminase (AST) (SGOT) and alanine transaminase (ALT) (SGPT)
≤2.5 x ULN if there is no evidence of liver metastasis or ≤5 x ULN in the presence of liver metastases.
* Albumin ≥ 30 g/L
* Adequate renal function: eGFR ≥ 50 ml/min
Exclusion Criteria:
1. Surgery or radiotherapy within \<3 weeks of registration. Patients must have recovered from any effects of any major surgery.
2. Any prior exposure to peptide receptor radionuclide therapy (177Lu, 111In or 90Y labelled), PARPi, immunotherapy
3. Uncontrolled intercurrent illness that is likely to impede participation and /or compliance
4. Other malignancies unless curatively treated with no evidence of disease within previous 3-years other than adequately treated non-melanoma skin cancer or melanoma in situ.
5. Previous or current history of myelodysplastic syndrome/acute myeloid leukemia
6. Patients unable to swallow orally administered medications or with gastrointestinal disorders likely to interfere with the absorption of the study medication.
7. Use of strong P-gp inhibitors (eg, dronedarone, quinidine, ranolazine, verapamil, ketoconazole, itraconazole), P-gp inducers (eg, rifampin, tipranavir/ritonavir), or BCRP inhibitors (eg, elacridar \[GF120918\]) should be avoided.
8. Participation in another clinical study with an investigational product or another systemic therapy administered in the last 3 weeks (except short acting SSA).
Where this trial is running
Melbourne, Victoria
- Peter MacCallum Cancer Centre — Melbourne, Victoria, Australia (Recruiting)
Study contacts
- Study coordinator: Grace Kong
- Email: NMResearch@petermac.org
- Phone: 85595000
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.